4-phenylpropyl-indoles having antiarythmic activity

Abstract

Novel 4-phenylpropyl-indoles of the formula <IMAGE> I wherein R and R1 are individually selected from the group consisting of hydrogen, linear alkyl of 1 to 5 carbon atoms, branched alkyl of 3 to 5 carbon atoms, cycloalkyl of 3 to 7 carbon atoms cycloalkylalkyl of 4 to 7 carbon atoms and optionally substituted aralkyl of 7 to 12 carbon atoms or R1 and R taken together with the nitrogen atom form an optionally unsaturated heterocycle containing another heteroatom selected from the group consisting of oxygen, sulfur and nitrogen optionally substituted with a member of the group consisting of alkyl of 1 to 5 carbon atoms, phenyl, naphthyl and aralkyl of 7 to 12 carbon atoms, a together with b forms =0 or a together with c form a carbon-carbon bond, b is hydrogen or with a forms =0, c is hydrogen or with a forms a carbon-carbon bond, the dotted line is an optional carbon-carbon bond, A is -(CH2)n-, is an integer from 2 to 5, R2 is selected from the group consisting of hydrogen, linear alkyl of 1 to 5 carbon atoms and branched alkyl of 3 to 5 carbon atoms, x is hydrogen or -OH or together with y forms =0 and y is hydrogen or together with x forms =0 and their non-toxic, pharmaceutically acceptable acid addition salts having remarkable antiarythmic properties and blocking of slow calcicosodic canals.

What is claimed is: 
     
       1. A compound selected from the group consisting of 4-phenyl propyl-indoles of the formula ##STR45## wherein R and R 1  are individually selected from the group consisting of hydrogen, linear alkyl of 1 to 5 carbon atoms, branched alkyl of 3 to 5 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, cycloalkylalkyl of 4 to 7 carbon atoms and aralkyl of 7 to 12 carbon atoms optionally substituted with 1 to 3 members of the group consisting of halogen, methyl, ethyl, methoxy, ethoxy, CF 3  --, CH 3  S--, --NH 2  and --NO 2  or R 1  and R taken together with the nitrogen atom form an heterocycle selected from the group consisting of pyrrolidino, piperidino, morpholino and piperazinyl optionally substituted with a member of the group consisting of alkyl of 1 to 5 carbon atoms, phenyl, naphthyl and aralkyl of 7 to 12 carbon atoms, a together with b forms ═0 or a together with c forms a carbon-carbon bond, b is hydrogen or with a forms ═0, c is hydrogen or with a forms a carbon-carbon bond, the dotted line is an optional carbon-carbon bond, A is --(CH 2 ) n  --, n is an integer from 2 to 5, R 2  is selected from the group consisting of hydrogen, linear alkyl of 1 to 5 carbon atoms and branched alkyl of 3 to 5 carbon atoms, x is hydrogen or --OH or together with y forms ═0 and y is hydrogen or together with x forms ═0 and their non-toxic, pharmaceutically acceptable acid addition salts. 
     
     
       2. A compound of claim 1 wherein a and c form a carbon-carbon bond. 
     
     
       3. A compound of claim 2 wherein R 1  and R 2  are both hydrogen. 
     
     
       4. A compound of claim 1 selected from the group consisting of N-[2-{2-(3-[1H-indol-4-yl]-propyl)-phenoxy}-ethyl]-2-methyl-2-propanamine and its non-toxic, pharmaceutically acceptable acid addition salts. 
     
     
       5. A compound of claim 1 selected from the group consisting of 1-[2-{3-(1,1-dimethylethylamino)-propoxy}-phenyl]-3-[1H-indol-4-yl]-1-propanone and its non-toxic, pharmaceutically acceptable acid addition salts. 
     
     
       6. A compound of claim 1 selected from the group consisting of N-[2-(2-{3-[1H-indol-4-yl]-propyl)-phenoxy}-ethyl]-N-isopropyl-2-propanamine and its non-toxic, pharmaceutically acceptable acid addition salts. 
     
     
       7. An antiarythmic composition comprising an antiarythmically effective amount of at least one compound of claim 1 and an inert pharmaceutical carrier. 
     
     
       8. A composition of claim 7 wherein in the compound a and c form a carbon-carbon bond. 
     
     
       9. A composition of claim 8 wherein in the compound R 1  and R 2  are both hydrogen. 
     
     
       10. A composition of claim 7 wherein the active compound is N-[2-{2-(3-[1H-indol-4-yl]-propyl)-phenoxy}-ethyl]-2-methyl-2-propanamine and its non-toxic, pharmaceutically acceptable acid addition salts. 
     
     
       11. A composition of claim 7 wherein the active compound is 1-[2-{3-(1,1-dimethylethylamino)-propoxy}-phenyl]-3-[1H-indol-4-yl]-1-propanone and its non-toxic, pharmaceutically acceptable acid addition salts. 
     
     
       12. A composition of claim 7 wherein the active compound is N-[2-(2-{3-[1H-indol-4-yl]-propyl)-phenoxy}-ethyl]-N-isopropyl-2-propanamine and its non-toxic, pharmaceutically acceptable acid addition salts. 
     
     
       13. A method of inducing antiarythmic activity in warm-blooded animals comprising administering to warm-blooded animals an antiarythmically effective amount of at least one compound of claim 1. 
     
     
       14. A method of claim 13 wherein in the active compound a and c form a carbon-carbon bond. 
     
     
       15. A method of claim 14 wherein in the active compound R 1  and R 2  are both hydrogen. 
     
     
       16. A method of claim 13 wherein the active compound is selected from the group consisting of N-[2-{2-(3-[1H-indol-4-yl]-propyl)-phenoxy}-ethyl]-2-methyl-2-propanamine and its non-toxic, pharmaceutically acceptable acid addition salts. 
     
     
       17. A method of claim 13 wherein the active compound is selected from the group consisting of 1-[2-{3-(1,1-dimethylethylamino)-propoxy}-phenyl]-3-[1H-indol-4-yl]-1-propanone and its non-toxic, pharmaceutically acceptable acid addition salts. 
     
     
       18. A method of claim 13 wherein the active compound is selected from the group consisting of N-[2-(2-{3-[1H-indol-4-yl]-propyl)-phenoxy}-ethyl]-N-isopropyl-2-propanamine and its non-toxic, pharmaceutically acceptable acid addition salts.